Sulfuric Acid → Ethyl 7-(4-ethylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate

Under argon atmosphere, to a solution of 4-ethylbromobenzene (10.0 g) in tetrahydrofuran (60 ml) was added n-butyllithium (1.6M hexane solution) (37.2 ml) at −78° C., and the mixture was stirred for 1 hour. To the reaction mixture was dropwise added a solution of tributyl borate (13.68 g) in tetrahydrofuran (30 ml), and the reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. To the reaction mixture was added 10% sulfuric acid (100 ml), and the mixture was stirred for 1 hour. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in acetone (30 ml), and to the mixture was added 10% sulfuric acid (50 ml). The mixture was stirred at room temperature for 16 hours, and under reduced pressure acetone was evaporated. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:2) to give crude 4-ethylphenyl borate(0.91 g) as colorless solid. Under argon atmosphere, a solution of ethyl 7-bromo-2,3-dihydro-1-benzoxepine-4-carboxylate (500 mg) the above crude 4-ethylphenyl borate (0.32 g) and potassium carbonate (0.49 g) in toluene-ethanol-water (20-2-2 ml) was stirred at room. temperature for 1 hour. To the reaction mixture was added tetrakistriphenyl-phosphinepalladium (0.06 g), and the mixture was refluxed for 18 hours and cooled to room temperature. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:15) to give ethyl 7—(4-ethylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate:(464 mg) as colorless crystals.

1. stirringstirred at room temperature for 2 hours
2. stirringthe mixture was stirred for 1 hour
3. extractionThe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with saturated sodium chloride solution
5. dry with materialdried with magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in acetone (30 ml)
8. additionto the mixture was added 10% sulfuric acid (50 ml)
9. stirringThe mixture was stirred at room temperature for 16 hours
10. customunder reduced pressure acetone was evaporated
11. extractionThe mixture was extracted with ethyl acetate
12. washThe organic layer was washed with saturated sodium chloride solution
13. dry with materialdried with magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe residue was separated
16. custompurified with column chromatography (ethyl acetate/hexane=1:2)
17. customto give crude 4-ethylphenyl borate(0.91 g) as colorless solid
18. waittemperature for 1 hour
19. temperaturethe mixture was refluxed for 18 hours
20. temperaturecooled to room temperature
21. washThe organic layer was washed with saturated sodium chloride solution
22. dry with materialdried with magnesium sulfate
23. concentrationconcentrated under reduced pressure
24. customThe residue was separated
25. custompurified with column chromatography (ethyl acetate/hexane=1:15)

ORD record

ord-2d1110878d924956b474e0ff6685da34

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06413947B1